Studies on the mutagenicity of divalent metals has shown that in addition to cobalt chloride (Co2+), ferrous sulfate (Fe2+), cadmium chloride (Cd2+), and zinc chloride (Zn2+), manganous sulfate (Mn2+), and nickel sulfate (Ni2+), are mutagenic in Salmonella typhimurium. Mutagenicity was detected only when preincubation was done in distilled, deionized water or HEPES buffer. Phosphate buffer or components of Vogel-Bonner medium, used in the standard mutagenicity studies, inhibited the mutagenicity of these metals. Studies of the specificity of mutagenesis in the different Salmonella strains have shown that metals can be detected as mutagens in both base- pair substitution and frameshift strains of Salmonella, and that the plasmid, pKM101, is required for mutagenesis. Under these same conditions, there was no evidence of mutagenicity for any of the lead (Pb2+) salts tested, and copper (Cu2+) salts produced equivocal responses. These data show that the traditional inability to detect these metals as mutagens in Salmonella is not due to an inherent insensitivity of the Salmonella, but to the interaction of the metals with media components and/or passive and active transport processes.